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Vitamin D and kidney stones

Chapter by: Mehta, Mansi; Goldfarb, David S.
in: Feldman and Pike's Vitamin D: Volume Two: Disease and Therapeutics by
[S.l.] : Elsevier, 2023
pp. 619-624
ISBN: 9780323913393
CID: 5622372


Kawakibi, A R; Tarapore, R; Gardner, S; Chi, A; Kurz, S; Wen, P Y; Arrillaga-Romany, I; Batchelor, T; Butowski, N; Sumrall, A; Shonka, N; Harrison, R; DeGroot, J; Mehta, M; Odia, Y; Hall, M; Daghistani, D; Cloughesy, T; Ellingson, B; Kim, M; Umemura, Y; Garton, H; Franson, A; Schwartz, J; Li, S; Cartaxo, R; Ravi, K; Cantor, E; Cummings, J; Paul, A; Walling, D; Dun, M; Cain, J; Li, J; Filbin, M; Zhao, L; Kumar-Sinha, C; Mody, R; Chinnaiyan, A; Kurokawa, R; Pratt, D; Venneti, S; Grill, J; Kline, C; Mueller, S; Resnick, A C; Nazarian, J; Waszak, S; Allen, J E; Koschmann, C
Patients with H3K27M-mutated diffuse midline glioma (DMG) have no proven effective therapies beyond radiation. ONC201, a DRD2 antagonist and mitochondrial ClpP agonist, has shown promise in this population. Clinical and genetic variables associated with ONC201 response in H3K27M-mutant DMG continue to be investigated. A combined clinical and genetic study evaluated patients with H3K27M-DMG treated with single-agent ONC201 at the established phase 2 dose. Clinical outcomes of patients treated on two recently completed multi-site clinical studies (NCT03416530 and NCT03134131, n = 75) were compared with historical control data from patients with confirmed H3K27M-DMG (n = 391 total, n = 119 recurrent). Patients treated with ONC201 monotherapy following initial radiation, but prior to recurrence, demonstrated a median overall survival (OS) of 25.6 months from diagnosis and recurrent patients demonstrated a median OS of 16.2 months from recurrence, both of these more than doubling historical outcomes. Using a Cox model to correct for age, gender and tumor location, OS of ONC201-treated patients with H3K27M-mutant tumors remained significantly better than non-ONC201-treated historical controls (p = 0.0001). A survival and radiographic analysis based on tumor location, revealed stronger responses in thalamic patients. In patients with thalamic tumors treated after initial radiation (n = 16), median OS was not reached with median follow up of 22.1 months (historical control median OS of 12.5 months, n = 83, p = 0.0001). Significant correlations were found between baseline cerebral blood flow (CBF) on perfusion imaging and OS (Pearson's r = 0.75, p = 0.003) and between nrCBF and PFS (r = 0.77, p = 0.002). Baseline tumor sequencing from treated patients (n = 20) demonstrates EGFR mutation (n = 3) and high EGFR expression as a marker of resistance and improved response in tumors with MAPK-pathway alterations (n = 5). In conclusion, ONC201 demonstrates unprecedented clinical and radiographic efficacy in H3K27M-mutant DMG with outcomes enriched in patients with thalamic tumors, treatment prior to recurrence, MAPKpathway alterations, and patients with relatively high CBF
ISSN: 1523-5866
CID: 5513292

A cascade of care for urinary stone disease (USD) [Meeting Abstract]

Mehta, M; Goldfarb, D S
Background: USD is a preventable disease characterized by significant risk of recurrence. A "cascade of care" shows how many patients are lost to follow-up at diagnosis, referral, and treatment and is a useful tool in delivering HIV care. We can analyze our success, or failure, in the secondary prevention of kidney stones and retention of patients by constructing a cascade of care.
Method(s): We abstracted data from observational studies to identify impediments to care of patients with USD Results: In the US there are about 1.2 million ER visits per year. 37% of patients diagnosed with stones receive a follow-up consultation with a urologist and fewer see a nephrologist. Although 24h urine collection results may decrease stone recurrence rate, only 7.4% do them. 50% of patients experience a recurrent 2nd episode within 5 years. Of these 24% undergo a complete evaluation, 18% are referred to a nephrologist and 13.8% are prescribed medical therapy. 30% remain adherent to this pharmacotherapy. Of patients that are adherent 27% have lower odds of an ER visit than non-adherent patients. The cascade of care demonstrates that a low prevalence of patients receive proper followup. The impediments to the care of patients with kidney stones are (1) the unrecognized comorbidities of stones (2) disconnect between the ER and stone experts and (3) the low prevalence of 24h urine collections and prescribed medical therapy.
Conclusion(s): It is important to identify loci in the cascade of care that could represent opportunities to change practice. Prescription of appropriate fluid therapy and dietary changes and a referral to an expert should 1st be initiated by the ER. The low prevalence of 24h urine collections may reflect that the data are intimidating for some. Empiric therapy for calcium stones with fluids, diet, thiazides and potassium citrate may be a rational therapy to achieve significant supersaturation reductions and could be compared with targeted medical therapy in a randomized controlled trial. A greater effort needs to be devoted to develp a comprehensive flow of participants to retain patients in the cascade of care for USD. (Table Presented)
ISSN: 1533-3450
CID: 4750222

The role of the microbiome in kidney stone formation

Mehta, Mansi; Goldfarb, David S; Nazzal, Lama
Nephrolithiasis is a complex disease of worldwide prevalence that is influenced by both genetic and environmental factors. About 75% of kidney stones are predominantly composed of calcium oxalate and urinary oxalate is considered a crucial risk factor. Microorganisms may have a role in the pathogenesis and prevention of kidney stones and the involvement of the intestinal microbiome in this renal disease has been a recent area of interest. Oxalobacter formigenes is a gram negative bacteria that degrades oxalate in the gut decreasing urinary oxalate excretion. In this review, we examine the data studying the role of Oxalobacter formigenes kidney stone disease in humans and animals, the effect of antibiotics on its colonization, and the potential role of probiotics and whole microbial communities as therapeutic interventions.
PMID: 27847292
ISSN: 1743-9159
CID: 2310952

Rewiring Redox-Sensitive GFP for Dynamic Imaging of Mycothiol Redox Potential in Mycobacterium Tuberculosis during Infection [Meeting Abstract]

Bhaskar, Ashima; Chawla, Manbeena; Mehta, Mansi; Parikh, Pankti; Chandra, Pallavi; Kumar, Dhiraj; Singh, Amit
ISSN: 0891-5849
CID: 3037812

Perceptions regarding barriers and facilitators to combination antiretroviral therapy adherence among people living with HIV/AIDS in Gujarat, India: A qualitative study

Patel, Sangita; Baxi, Rajendra K; Patel, Shilpa N; Golin, Carol E; Mehta, Mansi; Bakshi, Harsh; Shingrapure, Kalpita; Modi, Ekta; Coonor, Priyanka; Mehta, Kedar
OBJECTIVES/OBJECTIVE:To know the perceptions regarding barriers and facilitators to cART adherence among people living with HIV/AIDS MATERIALS AND METHODS: To adapt U.S. based SAFETALK "prevention with positives" intervention to be culturally relevant in Gujarat, India in assisting PLWHA, a formative study was conducted. We conducted 30 in-depth interviews with PLWHA in the local language, assessing the experiences, perceived barriers, and facilitators to combination antiretroviral therapy (cART) among PLWHA in Gujarat. PLWHA were selected from the Voluntary Counseling and Testing Centre (VCTC) in Gujarat. To triangulate interview findings, we conducted two focus group discussions (FGDs) with medical and non-medical providers, respectively. RESULTS:Travel and commuting to clinic, fear of possible physical reactions, high cost of ART from private practitioners, CD4 count being in normal limits and resistance to medication acted as barriers to cART adherence. Initiation of cART was facilitated by family members' suggestion, advice of treating doctors and counselors, appropriate counseling before starting cART, belief that cART would aid in living a better and longer life and due to lowering of the CD4 count. INTERPRETATION AND CONCLUSIONS/CONCLUSIONS:Our study suggests that several issues need to be considered when providing cART. Further research is needed to study interactions between patients and their health care providers.
PMID: 23188935
ISSN: 1998-3816
CID: 3037662

Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial

Spiera, Robert F; Gordon, Jessica K; Mersten, Jamie N; Magro, Cynthia M; Mehta, Mansi; Wildman, Horatio F; Kloiber, Stacey; Kirou, Kyriakos A; Lyman, Stephen; Crow, Mary K
OBJECTIVE:To assess the safety and effectiveness of imatinib mesylate in the treatment of diffuse cutaneous systemic sclerosis (dcSSc). METHODS:In this phase IIa, open-label, single-arm clinical trial, 30 patients with dcSSc were treated with imatinib 400 mg daily. Patients were monitored monthly for safety assessments. Modified Rodnan skin scores (MRSS) were assessed every 3 months. Pulmonary function testing, chest radiography, echocardiography and skin biopsies were performed at baseline and after 12 months of treatment. RESULTS:Twenty-four patients completed 12 months of therapy. 171 adverse events (AE) with possible relation to imatinib were identified; 97.6% were grade 1 or 2. Twenty-four serious AE were identified, two of which were attributed to study medication. MRSS decreased by 6.6 points or 22.4% at 12 months (p=0.001). This change was evident starting at the 6-month time point (Δ=-4.5; p<0.001) and was seen in patients with both early and late-stage disease. Forced vital capacity (FVC) improved by 6.4% predicted (p=0.008), and the diffusion capacity remained stable. The improvement in FVC was significantly greater in patients without interstitial lung disease. Health-related quality of life measures improved or remained stable. Blinded dermatopathological analysis confirmed a significant decrease in skin thickness and improvement in skin morphology. CONCLUSIONS:Treatment with imatinib was tolerated by most patients in this cohort. Although AE were common, most were mild to moderate. In this open-label experience, improvements in skin thickening and FVC were observed. Further investigation of tyrosine kinase inhibition for dcSSc in a double-blind randomised placebo controlled trial is warranted., NCT00555581.
PMID: 21398330
ISSN: 1468-2060
CID: 3037642

Activation of the type IIFN pathway in systemic sclerosis (SSc) is detected at the level of PBMC gene expression: Association with higher skin scores, inflammatory markers and anti-ro antibodies [Meeting Abstract]

MacDermott, Emma Jane; Barillas-Arias, Lilliana; Taimeh, Ziad A.; Santiago, Annie G.; Mehta, Mansi; Duculan, Roland; Spiera, Robert; Crow, Mary K.; Kirou, Kyriakos K.
ISSN: 0004-3591
CID: 3037782

Phase IIa trial of imatinib mesylate (Gleevec) in the treatment of diffuse systemic sclerosis - An interim analysis [Meeting Abstract]

Spiera, Robert F.; Gordon, Jessica K.; Mehta, Mansi; Kirou, Kyriakos A.; Lyman, Stephen; Kloiber, Stacey A.; Crow, Mary K.
ISSN: 0004-3591
CID: 3037792